This research program is concerned with the structure, metabolism and function of protein glycosaminoglycan complexes in normal individuals and individuals with connective tissue disease(s). Emphasis is divided between two major subprojects: 1) Mechanism of "correction" of protein-polysaccharide accumulation in cultured generalized gangliosidosis (GM1) skin fibroblasts. We have established that the carbohydrate portion of a mammalian lysosomal beta-galactosidase constitutes a portion of the recognition marker(s) for the assimilation of this enzyme by generalized gangliosidosis fibroblasts. We propose to continue to define the recognition marker(s) and to initiate studies designed to elucidate the (probable) fibroblast cell surface receptor. Studies are currently in progress to establish if other cell types including transformed cell lines assimilate beta-galactosidase in a similar fashion. 2) Anabolism and catabolism of proteoglycan protein-chondroitin sulfate-keratan sulfate complex. These efforts include studies concerned with the biosynthesis of the repeating disaccharide unit and the assembly of the oligosaccharide chains of keratan sulfate; emphasis is currently placed on how N-acetylglucosamine is incorporated into the repeating disaccharide unit. Catabolic studies continue to be concerned with the characterization of two endo-beta-galactosidases (keratinases) found in the species of marine mollusks and the use of these enzymes to elucidate the nature of the structure of the linkage region between the polypeptide core and the repeating disaccharide chain.